Characterization and identification of the key volatile and non-volatile substances of Vangueria madagascariensis J.F. Gmel fruits (Kirkir) and exploration of their binding interactions with olfactory and taste receptors using computational chemistry methodology.

Profiling of metabolites that contribute to the taste and odor of fruit products is important to produce the desired products. In this study, volatile and non-volatile compounds were analyzed using SPME/GC-MS and UHPLC-Q-Exactive-orbitrap-MS/MS, respectively. A total of 59 volatiles (including alcohols, aldehydes, acids, terpenes, ketones, phenols, and hydrocarbons et al.) and 18 non-volatiles (including phenolic acids, flavones, flavonoids, glucosides, phenols, and quinic acid derivatives et al.) were detected in dried Kirkir fruits. The binding interactions between the key volatiles and the detected non-volatiles with taste and olfactory receptors were also evaluated. Based on the molecular docking, 11 volatile compounds may contribute to the overall odor, while 16 non-volatile compounds may contribute to the taste of the Kirkir fruits. In conclusion, in silico studies can serve as a powerful technique for understanding mechanisms of interaction and predicting the key phytochemicals that contribute to the odor and taste of fruits.

Fear of a new pandemic: perception and prediction of monkeypox among the middle east general population.

Background: Monkeypox is a zoonotic disease caused by the monkeypox virus, an Orthopox virus. The 2022 monkeypox outbreak provoked fear among the public. Public awareness about the disease could be an important factor in its control. The authors conducted this study to assess the perception and prediction of monkeypox among the Middle East public. Methods: This cross-sectional study was conducted in August 2022. Data were conveniently collected from eight Middle Eastern countries using an online self-administered questionnaire distributed through educational and social media platforms. Statistical analysis was conducted using R software. Results: Approximately 11 016 individuals participated in this study. The participants' overall knowledge score indicated poor knowledge about monkeypox. Most of the participants knew the causative organism (66.7%). However, numerous participants were not aware of the disease mode of transmission, symptoms, complications, and vaccination. Participants' awareness was mostly gained from social media (61.8%). The majority predicted acquiring monkeypox when protective measures are not taken (72.7%), progression to a pandemic with economic consequences (50.8 and 52%, respectively), and the ability of the Ministry of Health to control the epidemic (51.5%). Conclusion: In the Middle East, public knowledge about monkeypox is poor. Raising awareness about monkeypox would be of benefit in controlling the epidemic. This study constitutes evidence upon which health education programs could be designed.

Optimization of topical curcumin spanlastics for melanoma treatment.

The aim of the study was to enhance curcumin skin permeability through the preparation of spanlastics. Spanlastics were prepared using the ethanol injection technique through a central composite design using Span 60 concentration (X1), edge activator type (X2), and its concentration (X3) as the independent variables. The spanlastics were characterized for particle size (PS), encapsulation efficiency (EE), and dissolution efficiency (%DE24h). Formulae with the highest desirability (FN1 and FN2) were prepared and further characterized. They were elastic, spherical, nonirritant, and compatible with the used excipients. They had particle sizes of 147 and 198 nm, encapsulation efficiencies of 84.00% and 89.63%, zeta potential values of -45.50 and -39.10 mV, permeation enhancement ratios of 11.51 and 8.34 folds, and amounts retained of 7.25 and 10.44 µg/cm2 after 24 h, respectively. Formulae FN1 and FN2 showed cytotoxic effects after 48 h on human melanoma A375 with IC50 of 10.9 and 75.6 µg/mL, respectively. They increased the apoptotic effect confirming the success of the spanlastics to be a potential delivery for melanoma treatment.

Application of mathematical modelling to alginate chitosan polyelectrolyte complexes for the prediction of system behavior with Venlafaxine HCl as a model charged drug.

Purpose: This work aimed to develop and analyze the performance of chitosan/alginate polyelectrolyte complex (PEC). Multiple regression and Lab fit curve fitting were applied to derive empirical models for the prediction of zeta potential of plain systems as a function of alginate chitosan ratio. Venlafaxine-HCl was loaded as a model charged drug and empirical models for prediction of its release as a function of time were also derived. Methods: Coacervation method was used for the preparation of green PECs. Preliminary studies were conducted to optimize the preparation method. Pre-adjustment of the pH of alginate and chitosan sols enabled the formation of PECs at alginate/chitosan ratios starting from 1:9 to 9:1. On mixing of alginate and chitosan sols, equal volume dilution method produced spherical particles, while direct mixing method gave fibrous particles. Twenty-seven PECs nanoparticle formulae were prepared using nine alginate/chitosan ratios and three levels of total polymer concentrations. Results: Statistical analysis showed that Zeta potential of the nanoparticle was significantly dependent on alginate/chitosan ratio, while particle size was a function of total polymer concentration. Nine fiber formulae were prepared and evaluated for their appearance and zeta potential. Venlafaxine-HCl release followed anomalous transport mechanism. FT-IR and DSC studies confirmed complexation at the carboxylate and amine site at alginate and chitosan respectively. Conclusion: Chitosan/alginate PECs were successfully obtained without a cross-linker and empirical equations were obtained to help finding the best composition for loading charged drugs and to predict their release profiles.

Diacerein solid dispersion loaded tablets for minimization of drug adverse effects: statistical design, formulation, in vitro, and in vivo evaluation.

Diacerein is a BCS class II drug employed in osteoarthritis management. The acid/base hydrolysis of the unabsorbed diacerein in the colon is responsible for its laxative effect. Therefore, this work aimed to enhance the solubility, dissolution, and oral bioavailability of diacerein. Such enhancement means lower doses and fewer gastrointestinal adverse effects. A 41.31.21 full factorial design was adopted to prepare 24 solid dispersion formulae. Solid-state characterization showed the dissolution of diacerein crystals as metastable amorphous or microcrystalline forms in a matrix system that enhanced the drug dissolution. Desirability factor suggested compounding an optimized formula (F1) of Pluronic®F68 with 1:3 drug:carrier ratio using rotavap that showed higher drug solubility (187.61 µg/mL) than drug powder (22.5 µg/mL). It achieved higher dissolution efficiency (4.04-fold) and rate (6.6-fold) as well as 100% release in 2 min. F1 was compressed into tablets recording greater dissolution efficiency (1.24-fold) and rate (12.5-fold) than the marketed product. The prepared tablet accomplished a 2.66-fold enhancement in diacerein bioavailability compared to the marketed product. In conclusion, the formulation of diacerein as solid dispersion loaded tablets could be of added value for the treatment of osteoarthritis in terms of enhanced patient compliance. Solid dispersion is an easy and scalable technique.

Formulation of sustained release bioadhesive minitablets containing solid dispersion of levofloxacin for once daily ocular use.

This study aimed to increase ocular residence time of levofloxacin by formulation into zero-order sustained release mucoadhesive minitablets for once daily administration using a hydrophobic-hydrophilic polymeric matrix. Levofloxacin was first formulated into solid dispersion with different ratios of Eudragit® RS then the resulting solid dispersion was mixed with different concentrations of Carbopol® and other excipients to be finally compressed into minitablets. A 24 full factorial design was employed to estimate the effects and interactions of two formulation factors, and to establish their relationships with selected responses in the developed minitablets. The studied factors were: drug to Eudragit® RS ratio, and percent of Carbopol® in the minitablets. Sixteen ocular minitablets formulations were prepared and evaluated for the cumulative percentages drug release at 6, 12, and 24 h, as well as mucoadhesion time, mucoadhesive strength, and swelling index as response variables. After optimizing the responses, the optimized formulation was found to be stable on sterilization using gamma-irradiation and storage at 40 °C/75% RH for six months. In vivo testing of the optimized formulation showed that the minitablets extended levofloxacin release up to 24 h without causing any ocular irritation. The optimized formulation exhibited superior microbiological activity compared to the commercial product.

Solid Form of Lipid-Based Self-Nanoemulsifying Drug Delivery Systems for Minimization of Diacerein Adverse Effects: Development and Bioequivalence Evaluation in Albino Rabbits.

This work aimed to enhance the oral bioavailability of diacerein. The drug was incorporated in self-nanoemulsifying drug delivery system. Ternary phase diagrams were constructed using Capryol™90, Miglyol®812 and isopropyl myristate as oils, Tween®80 and Tween®20 as surfactants and PEG 200 and PEG 300 as co-surfactants. Among a total of 432 formulae, 17 formulae were clear. They were assessed for mean droplet size, polydispersity index (PDI), saturation solubility and transmission electron microscopy. Solid granules were obtained by adsorption on Aeroperl®300. Results for DSC, PXRD, and SEM of prepared granules revealed that diacerein was molecularly dispersed within the formula. Desirability factor was adopted to find the granules with maximum solubility, maximum dissolution efficiency, maximum dissolution rate and percentage of drug dissolved at 5 min and minimum dissolution time and Carr's index. The optimized formula consisted of 10% Miglyol®812, 70% Tween®80 and 20% PEG 200 adsorbed to Aeroperl® 300 with a ratio of 2:1 preconcentrate:carrier. It recorded a 3.77-fold increase in bioavailability, compared to the marketed product. Such enhancement means lower doses and less gastrointestinal side effects.

Effects of different combinations of nanocrystallization technologies on avanafil nanoparticles: in vitro, in vivo and stability evaluation.

The study investigated the effects of different combined top-down and bottom-up nanocrystallization technologies on particle size and solid state of avanafil nanoparticles. Combined antisolvent precipitation-ultrasonication (sonoprecipitation) technique was adopted to prepare 18 formulas according to 32.21 factorial design using 3 stabilizers; Tween 80, polyvinyl alcohol (PVA) and Pluronic F68 at different concentrations with different cryoprotectants. Particle size analysis of the lyophilized formulas showed that Tween 80 was an effective nanoparticles stabilizer in contrast to Pluronic F68 and PVA which failed to prevent nanoparticles flocculation when they were used at high concentration. The combined effects of nanonization and amorphism contributed to the improvement in solubility. Further processing of the sonoprecipitated formulas by high pressure homogenization (HPH) (modified NANOEDGE™ technology) resulted in further size reduction of PVA-stabilized particles, while it stimulated flocculation of Tween-stabilized nanoparticles. Nevertheless, all of the homogenized formulas partially retrieved their crystallinity which reduced their solubility. Non-homogenized formula 2E composed of 1:2 (avanafil: Tween) with glucose as cryoprotectant, exhibited 13.68- and 2.59-fold improvement in solubility and in vitro dissolution, respectively. This formula had oral bioavailability of 137.02% relative to Spedra® tablets and it maintained its nanosize, amorphism and dissolution behavior over 6 months of storage under stress conditions.

Effect of different polymers on avanafil-ß-cyclodextrin inclusion complex: in vitro and in vivo evaluation.

In this study, we examined the effect of different polymers on the chemical, physical and pharmacokinetic properties of avanafil-ß-cyclodextrin (ß-CD) inclusion complex. Equimolar mixtures of drug and ß-CD were used to prepare 25 ternary drug-ß-CD-polymer inclusion complexes using five different polymers, polyethylene glycol (PEG 4000), polyvinyl pyrrolidone (PVP K-30), chitosan, hydroxypropylmethyl cellulose, and hydroxyethyl cellulose, each in five different concentrations, 1, 3, 5, 7, and 10% (w/w). The addition of 10% (w/w) PEG 4000 resulted in a significant decrease of drug solubility, where the infrared spectra and differential scanning thermograms revealed an interaction between PEG 4000 and avanafil which hindered drug inclusion. In contrast, addition of 7% (w/w) PVP K-30 facilitated drug inclusion as concluded from differential scanning thermograms, X-ray diffraction patterns and scanning electron micrographs. This resulted in a subsequent improvement in drug solubility and in vitro dissolution. This formula was chemically and physically stable for 6 months under accelerated storage conditions. The formula had a relative bioavailability of 125.56% in rabbits as compared to conventional commercially available avanafil tablets (Spedra(®)).

Formulation of avanafil in a solid self-nanoemulsifying drug delivery system for enhanced oral delivery.

Avanafil was incorporated into solid self-nanoemulsifying systems with the aim of improving its oral bioavailability. Labrafil, Labrafac, and Miglyol 812 N were investigated as oils, Tween 80 and Cremophor EL as surfactants, and Transcutol HP as a co-surfactant. Nine formulations produced clear solutions of 13.89-38.09nm globules after aqueous dilution. Adsorption of preconcentrate onto Aeroperl 300 Pharma at a 2:1 ratio had no effect on nanoemulsion particle size. Differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy indicated that avanafil was molecularly dispersed within the solid nanosystems. A formulation containing 10% Labrafil, 60% Tween 80, and 30% Transcutol HP had the highest drug loading (44.48mg/g) and an acceptable in vitro dissolution profile (96.42% within 30min). This formulation was chemically and physically stable for 6months under accelerated storage conditions and it produced a 3.2-fold increase in bioavailability in rabbits, as compared to conventional commercially available avanafil tablets (Spedra(®)).

Formulation of venlafaxine for once daily administration using polymeric material hybrids.

OBJECTIVE: Controlled release venlafaxine for once daily administration. METHODS: Drug resin complexation followed by polymer encapsulation. A 4(1).2(1) factorial design was used to study the effect of polymer type and core: coat ratio on the release profile and kinetics. Polymer combinations were tried for optimisation adapting the desIMNCility function. The optimised formula was tested in rabbits against commercial extended release capsules. RESULTS: Poly-epsilon-caprolactone, poly(d, l-lactide-co-glycolide) ester and poly(d, l-lactide) ester polymers were more efficient in lowering the release rate and the initial burst release than Eudragit(®)RS100. Encapsulation at 1:1 ratio ensured complete coats and drug release sustainment. Formula prepared using 50:50 PLA/Eudragit at 1:1 ratio sustained the drug release up to 24 h with low burst release. This formula had higher venlafaxine absorption in rabbits compared to the commercial capsules. CONCLUSIONS: The optimised formula is superior to the available once-daily trials regarding enhanced bioavailability, dosage form versatility and ease of scaling up.

Localized rosuvastatin via implantable bioerodible sponge and its potential role in augmenting bone healing and regeneration.

OBJECTIVE: Statins proved potential bone healing properties. Rosuvastatin is a synthetic, hydrophilic, potent and highly efficacious statin. In the current work, an attempt was investigated to develop, evaluate various bioerodible composite sponges enclosing rosuvastatin and explore their potential in augmenting bone healing and regeneration. METHOD: Twelve lyophilized sponge formulae were prepared adapting a 41.31 full factorial design. Xanthan gum, polycarbophil, Carbopol® and sodium alginate were investigated as anionic polymers, each at three chitosan:anionic polymer ratios (1:3, 1:1, 3:1). The formula of choice was implanted in fractured rat femora. RESULTS: Visual and microscopic examination showed flexible homogenous porous structures with considerable bending ability. Polyelectrolyte complex formation was proved by DSC and FT-IR for all chitosan/anionic combinations except with xanthan gum where chitosan probably bound to the drug rather than xanthan gum. Statistical analysis proved that anionic polymer type and chitosan: polymer ratio, as well as, their interactions, exhibited significant effects on the release parameters at p ≤ 0.05. The optimum chitosan/anionic polymer complexation ratios were 3:1 for polycarbophil and 1:1 for Carbopol and alginate. The release at these ratios followed Fiction diffusion while other ratios had anomalous diffusion. Imwitor® 900K and HPMC K100M were added as release retarardants for further release optimization. The formula of choice was implanted in fractured rat femora. Histopathological examination revealed advanced stages of healing in treated femora compared to control ones. CONCLUSION: Biodegradable sponges for local rosuvastatin delivery proved significantly enhanced wound healing and regeneration properties to fractured bones.

Effervescent tablet formulation for enhanced patient compliance and the therapeutic effect of risperidone.

Risperidone is a poorly water soluble atypical antipsychotic drug. This work investigated the potential of developing risperidone effervescent tablets to facilitate drug administration and mask drug taste. The solid dispersion technique was selected to improve drug solubility due to its ease of scaling up, reproducibility and affordable cost. Thirty formulas were prepared adopting a 5(1).2(1).3(1) full factorial design. Trehalose, Inulin, pregelatinized starch, carboxymethylcellulose sodium and Eudragit E100 were used as hydrophilic carriers at different ratios. Rotovap, lyophilization and the kneading-oven were applied as solvent evaporation techniques. Differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy showed that the drug was present as amorphous material entrapped within the carrier matrix. Eight tablet blends were prepared using different effervescent mixture ratios with or without binder and lubricant/glidant mixture. All of the blends had acceptable flowability, acceptable effervescence times and immediate drug release that could not be achieved by any of the control formulas. The formula of choice contained 40% effervescent mixture, 5% starch, 1% boric acid, 1% aspartame and sufficient lactose. The relative bioavailability (RB) of risperidone from this formula was 161.41% with a significantly higher extent of absorption compared to the market conventional tablets. This formula may be promising in improving patient compliance and drug efficiency.

Formulation of Convenient, Easily Scalable, and Efficient Granisetron HCl Intranasal Droppable Gels.

Deacetylated gellan gum and two sodium alginate polymer types were used each at three concentrations in the suitable range for their sol-gel transition. The prepared nine droppable gels were evaluated in vitro, ex vivo through sheep nasal mucosa, as well as in vivo in comparison to drug solution given intravenously and orally at the same dose. The prepared formulas gelled instantaneously in simulated nasal fluid and the obtained gels sustained their shear thinning and thixotropic behavior up to 48 h. Polymer type and concentration had significant effects on the apparent viscosities and the in vitro release profile of granisetron from the prepared gels. The drug release data best fitted a modified Higuchi equation with initial burst and followed Fickian diffusion mechanism. A 0.5% gellan-gum-based formula sustained the in vitro drug release up to 3 h and enhanced the drug permeation without need for an enhancer. The histopatholgical study revealed the safety of the tested formula. Intranasal delivery recorded double the drug bioavailabilty in comparison to the oral route. It had an absolute bioavailability of 0.6539 and the maximum plasma drug concentration reached after 1.5 h. The developed formula could be promising for the management of chemotherapy-induced nausea and vomiting regarding its improved bioavailability, patient acceptability, and ease of production.

In vitro and in vivo evaluation of indomethacin nanoemulsion as a transdermal delivery system.

Nanoemulsions were investigated as transdermal delivery systems for indomethacin. Six formulae were prepared using Triacetin, capryol 90 and labrafil as oils; Tween 80 and pluronic F127 as surfactants and transcutol and propylene glycol as co-surfactants. The continuous phase was that one with the larger volume fraction regardless of the hydrophile-lipophile balance of the surfactant/co-surfactant mixture. Surfactant type had significant effects on particle size and rheological properties of the nanoemulsions. Pluronic-based formulae recorded the lowest particle sizes and the highest viscosities. The prepared nanoemulsions increased drug solubility up to 610-fold compared with water. Refractive index measurements proved the compatibility between indomethacin and the used nanoemulsion components. Indomethacin was almost completely ionized at the pH values of the prepared nanoemulsions, suggesting drug absorption via the hydrophilic pathway of the skin upon topical application. Nanoemulsions controlled indomethacin release through semipermeable membrane and enhanced its permeation through excised newly born albino rat skin. The formulae were stable for six months at ambient conditions. Transdermal single application of selected formulae resulted in effective plasma levels up to 32 h in rats. Nanoemulsions were significantly superior to other investigated transdermal approaches at solubilizing indomethacin and achieving higher plasma levels.

Fast-dissolving sublingual films of terbutaline sulfate: formulation and in vitro/in vivo evaluation.

Terbutaline sulfate fast dissolving sublingual films were prepared using seven drug compatible film formers in different combinations and proportions. The film polymers are maltodextrin, Na alginate, Carpabol 430, xanthan gum, HPMC E5, PVP K-25, and Na CMC. Propylene glycol and sorbitol were used as plasticizers and mannitol as filler. The optimum polymer concentrations and the plasticizer amount were selected on the basis of flexibility, tensile strength, and stickiness of the films. The prepared films were evaluated for their tensile strength, thickness uniformity, disintegration time (in vitro and in vivo), in vitro dissolution, and moisture content. Polymer type rather than total polymer concentration or plasticizer amount showed a significant effect on the tested film properties. A randomized, single dose, crossover study was conducted in four healthy volunteers to compare the pharmacokinetic profile of terbutaline sulfate from the prepared films and the conventional oral tablets. The film formula of choice gave a significantly faster drug absorption rate and recorded a relative bioavailability of 204.08%. Sublingual films could be promising as a convenient delivery system for terbutaline sulfate in patients with swallowing problems. The improved extent of absorption (higher AUC(0-24)) indicates success in improving drug bioavailability, and the faster absorption rate could be promising for the management of acute episodes of asthma.

Microemulsions as vehicles for topical administration of voriconazole: formulation and in vitro evaluation.

This work was undertaken to investigate microemulsion (ME) as a topical delivery system for the poorly water-soluble voriconazole. Different ME components were selected for the preparation of plain ME systems with suitable rheological properties for topical use. Two permeation enhancers were incorporated, namely sodium deoxycholate or oleic acid. Drug-loaded MEs were evaluated for their physical appearance, pH, rheological properties and in vitro permeation studies using guinea pig skin. MEs based on polyoxyethylene(10)oleyl ether (Brij 97) as the surfactant showed pseudoplastic flow with thixotropic behavior and were loaded with voriconazole. Jojoba oil-based MEs successfully prolonged voriconazole release up to 4 h. No significant changes in physical or rheological properties were recorded on storage for 12 months at ambient conditions. The presence of permeation enhancers favored transdermal rather than dermal delivery. Sodium deoxycholate was more effective than oleic acid for enhancing the voriconazole permeation. Voriconazole-loaded MEs, with and without enhancers, showed significantly better antifungal activity against Candida albicans than voriconazole supersaturated solution. In conclusion, the studied ME formulae could be promising vehicles for topical delivery of voriconazole.

Enhancement of the intranasal delivery of insulin via a novel mucoadhesive Carbopol gel.

OBJECTIVES: The objectives of this study were to develop an intranasal insulin gel using Carbopol homogenization rather than neutralization and to examine the effectiveness of the gel compared with a subcutaneous injection. METHODS: Four factors, namely the molecular weight of polyethylene glycol (PEG), the concentration of Carbopol, the temperature of preparation and the type of absorption enhancer, were evaluated for their effect on viscosity and in-vitro insulin release. Bioavailability of insulin from selected formulations was compared with an intranasal solution and subcutaneous injection in rabbits. KEY FINDINGS: Increasing the molecular weight of PEG and Carbopol concentration increased the gel viscosity and changed the release mechanism from diffusion to case II transport. Applying heat during preparation resulted in a lower viscosity gel and increased the in-vitro insulin release. Among the two enhancers studied, sodium deoxycholate resulted in a higher viscosity gel than Tween 80. In vivo, the intranasal gel showed a stronger and longer hypoglycaemic effect with 1.7- and 3.1-fold higher maximum decrease in blood glucose level and area above the curve, respectively, compared with the subcutaneous injection. CONCLUSIONS: The homogenized Carbopol intranasal gel could be an efficient noninvasive way for insulin delivery but selection of gel components and method of preparation are critical for achieving the most desired effect.

Mucoadhesive nanoparticles as carrier systems for prolonged ocular delivery of gatifloxacin/prednisolone bitherapy.

A fluoroquinolone/glucocorticoid combination for the treatment of bacterial keratitis in the form of mucoadhesive nanoparticle suspensions was developed to prolong the release and improve patient compliance. Gatifloxacin/prednisolone loaded nanoparticles were prepared using Eudragit RS 100 and RL 100 and coated with the bioadhesive polymer, hyaluronic acid. FT-IR and DSC studies revealed no interaction between gatifloxacin and prednisolone. The effects of the drug:polymer ratio (D:P) and the RS/RL ratio were studied. The obtained nanoparticles were distinct and spherical with a solid dense structure. They have average particle size range of 315.2 to 973.65 nm. Increasing the D:P ratio significantly lowered the entrapment efficiency for both drugs (p < 0.05). The nanoparticle suspensions revealed significantly prolonged drug release comparing to the free drugs (p < 0.05) with no burst effect. Increasing the polymer concentration and the Eudragit RS ratio significantly decreased the release efficiency values. Gatifloxacin showed anomalous release (n = 0.4943) from 1:1 D:P ratio nanoparticle suspension and Fickian diffusion mechanism (n < 0.45) from formulas prepared at higher D:P ratios. Gatifloxacin showed better bioavailability and sustained action in aqueous humor and corneal tissue from the nanoparticles compared to the commercial eye drops. The resulting nanoparticle suspension is promising in reducing dose frequency and improving patient compliance.

Valsartan orodispersible tablets: formulation, in vitro/in vivo characterization.

Valsartan orodispersible tablets have been developed at 40-mg dose, with the intention of facilitating administration to patients experiencing problems with swallowing and hopefully, improving its poor oral bioavailability. Work started with selecting drug compatible excipients depending on differential scanning calorimetric analysis. A 3(3) full factorial design was adopted for the optimization of the tablets prepared by freeze-drying technique. The effects of the filler type, the binder type, and the binder concentration were studied. The different tablet formulas were characterized for their physical properties, weight variation, disintegration time, surface properties, wetting properties, and in vitro dissolution. Amongst the prepared 27 tablet formulas, formula number 6 (consisting of 4:6 valsartan:mannitol and 2% pectin) was selected to be tested in vivo. Oral bioavailability of two 40 mg valsartan orodispersible tablets was compared to the conventional commercial tablets after administration of a single dose to four healthy volunteers. Valsartan was monitored in plasma by high-performance liquid chromatography. The apparent rate of absorption of valsartan from the prepared tablets (C (max) = 2.879 microg/ml, t (max) = 1.08 h) was significantly higher than that of the conventional tablets (C (max) = 1.471 microg/ml, t (max) = 2.17 h), P < or = 0.05. The relative bioavailability calculated as the ratio of mean total area under the plasma concentration-time curve for the orodispersible tablets relative to the conventional ones was 135%. The results of the in vivo study revealed that valsartan orodispersible tablets would be advantageous with regards to improved patient compliance, rapid onset of action, and increase in bioavailability.